Photoionization in the time and frequency domain Isinger, M.; Squibb, R. J.; Busto, D. ...
Science (American Association for the Advancement of Science),
11/2017, Letnik:
358, Številka:
6365
Journal Article
Recenzirano
Odprti dostop
Ultrafast processes in matter, such as the electron emission after light absorption, can now be studied using ultrashort light pulses of attosecond duration (10−18 seconds) in the extreme ultraviolet ...spectral range. The lack of spectral resolution due to the use of short light pulses has raised issues in the interpretation of the experimental results and the comparison with theoretical calculations. We determine photoionization time delays in neon atoms over a 40–electron volt energy range with an interferometric technique combining high temporal and spectral resolution. We spectrally disentangle direct ionization from ionization with shake-up, in which a second electron is left in an excited state, and obtain excellent agreement with theoretical calculations, thereby solving a puzzle raised by 7-year-old measurements.
Electron dynamics induced by resonant absorption of light is of fundamental importance in nature and has been the subject of countless studies in many scientific areas. Above the ionization threshold ...of atomic or molecular systems, the presence of discrete states leads to autoionization, which is an interference between two quantum paths: direct ionization and excitation of the discrete state coupled to the continuum. Traditionally studied with synchrotron radiation, the probability for autoionization exhibits a universal Fano intensity profile as a function of excitation energy. However, without additional phase information, the full temporal dynamics cannot be recovered. Here we use tunable attosecond pulses combined with weak infrared radiation in an interferometric setup to measure not only the intensity but also the phase variation of the photoionization amplitude across an autoionization resonance in argon. The phase variation can be used as a fingerprint of the interactions between the discrete state and the ionization continua, indicating a new route towards monitoring electron correlations in time.
Introduction
The likelihood of survival after cancer treatment among young women with cancer has increased considerably, quality of life after treatment has drawn more attention. However, in young ...fertile women, fertility preservation is an important issue with regard to quality of life. One of the options of fertility preservation is ovarian tissue cryopreservation. The purpose of this follow‐up study is to present our clinical experiences and evaluate the long‐term follow up of ovarian cryopreservation to improve future patient selection.
Material and methods
From July 2002 to December 2015 at the Leiden University Hospital, the Netherlands, 69 young women underwent ovarian tissue cryopreservation when they were at risk of iatrogenic premature ovarian insufficiency. Follow‐up data with regard to ovarian function were obtained until October 2018, from medical records and questionnaires.
Results
Of the 69 women in whom ovarian tissue cryopreservation was performed, 12 died (15.9%), 57 were approached to participate, of which 6 were lost to follow up. The indications for ovarian tissue cryopreservation were malignant (81.1%) and benign (18.9%) diseases in which gonadotoxic treatment was scheduled. In total, twenty women (39.2%) are known to have premature ovarian insufficiency due to gonadotoxic treatment. Fifteen women conceived spontaneously, and delivered 25 babies. In this cohort, the usage rate of autotransplantation is 8.7% (7/69). In total, nine autotransplantations of cryopreserved ovarian tissue were performed in seven patients (of which 1 ovarian tissue cryopreservation was performed in another hospital) after which 6 babies were born to four women, giving a live‐birth rate of 57%.
Conclusions
Ovarian tissue cryopreservation followed by autotransplantation is an effective method to restore fertility (live‐birth rate of 57%). The usage rate of 8.7% (6/69) indicates that more knowledge about the risk of premature ovarian insufficiency after gonadotoxic treatment is needed to be able to offer ovarian tissue cryopreservation more selectively.
Galectins are proteins that bind β-galactoside sugars and provide a new type of potential biomarkers and therapeutic targets in cancer. Galectin-1, -3 and -9 have become the focus of different ...research groups, but their expression and function in cervical cancer is still unclear. The aim of this study was to determine the phenotype of galectin-1, -3 and -9 expressing cells and the association with clinico-pathological parameters in cervical cancer. Galectin expression was scored in tumor cells, tumor epithelium infiltrating immune cells and stromal cells in squamous cervical cancer (n = 160). Correlations with clinico-pathological parameters and survival were studied according to the REMARK recommendations. We additionally investigated whether the galectins were expressed by tumor cells, fibroblasts, macrophages and T cells. Galectin-1 and -9 were both expressed by tumor cells in 11% of samples, while 84% expressed galectin-3. Strong galectin-1 expression by tumor cells was an independent predictor for poor survival (hazard ratio: 8.02, p = 0.001) and correlated with increased tumor invasion (p = 0.032) and receiving post-operative radiotherapy (p = 0.020). Weak and positive tumor cell galectin-3 expression were correlated with increased and decreased tumor invasion, respectively (p = 0.012). Tumor cell expression of galectin-9 showed a trend toward improved survival (p = 0.087). The predominant immune cell type expressing galectin-1, -3 and -9 were CD163+ macrophages. Galectin-1 and -3 were expressed by a minor population of T cells. Galectin-1 was mainly expressed by fibroblasts in the tumor stroma. To conclude, while tumor cell expression of galectin-9 seemed to represent a beneficial response, galectin-1 expression might be used as a marker for a more aggressive anti-cancer treatment.
In ovarian cancer, two of the most important prognostic factors for survival are completeness of staging and completeness of cytoreductive surgery. Therefore, intra-operative visualization of tumor ...lesions is of great importance. Preclinical data already demonstrated tumor visualization in a mouse-model using near-infrared (NIR) fluorescence imaging and indocyanine green (ICG) as a result of enhanced permeability and retention (EPR). The aim of this study was to determine feasibility of intraoperative ovarian cancer metastases imaging using NIR fluorescence imaging and ICG in a clinical setting.
Ten patients suspected of ovarian cancer scheduled for staging or cytoreductive surgery were included. Patients received 20 mg ICG intravenously after opening the abdominal cavity. The mini-FLARE NIR fluorescence imaging system was used to detect NIR fluorescent lesions.
6 out of 10 patients had malignant disease of the ovary or fallopian tube, of which 2 had metastatic disease outside the pelvis. Eight metastatic lesions were detected in these 2 patients, which were all NIR fluorescent. However, 13 non-malignant lesions were also NIR fluorescent, resulting in a false-positive rate of 62%. There was no significant difference in tumor-to-background ratio between malignant and benign lesions (2.0 vs 2.0; P=0.99).
This is the first clinical trial demonstrating intraoperative detection of ovarian cancer metastases using NIR fluorescence imaging and ICG. Despite detection of all malignant lesions, a high false-positive rate was observed. Therefore, NIR fluorescence imaging using ICG based on the EPR effect is not satisfactory for the detection of ovarian cancer metastases. The need for tumor-specific intraoperative agents remains.
ISRCTN Registry ISRCTN16945066.
Recent studies have shown that 7% to 12% of endometrial cancers are ultramutated due to somatic mutation in the proofreading exonuclease domain of the DNA replicase POLE. Interestingly, these tumors ...have an excellent prognosis. In view of the emerging data linking mutation burden, immune response, and clinical outcome in cancer, we investigated whether POLE-mutant endometrial cancers showed evidence of increased immunogenicity.
We examined immune infiltration and activation according to tumor POLE proofreading mutation in a molecularly defined endometrial cancer cohort including 47 POLE-mutant tumors. We sought to confirm our results by analysis of RNAseq data from the TCGA endometrial cancer series and used the same series to examine whether differences in immune infiltration could be explained by an enrichment of immunogenic neoepitopes in POLE-mutant endometrial cancers.
Compared with other endometrial cancers, POLE mutants displayed an enhanced cytotoxic T-cell response, evidenced by increased numbers of CD8(+) tumor-infiltrating lymphocytes and CD8A expression, enrichment for a tumor-infiltrating T-cell gene signature, and strong upregulation of the T-cell cytotoxic differentiation and effector markers T-bet, Eomes, IFNG, PRF, and granzyme B. This was accompanied by upregulation of T-cell exhaustion markers, consistent with chronic antigen exposure. In silico analysis confirmed that POLE-mutant cancers are predicted to display more antigenic neoepitopes than other endometrial cancers, providing a potential explanation for our findings.
Ultramutated POLE proofreading-mutant endometrial cancers are characterized by a robust intratumoral T-cell response, which correlates with, and may be caused by an enrichment of antigenic neopeptides. Our study provides a plausible mechanism for the excellent prognosis of these cancers.
Background This study was conducted to assess the accuracy and feasibility of diagnostic hysteroscopy in the evaluation of intrauterine abnormalities in women with abnormal uterine bleeding.
Search ...strategy Electronic databases were searched from 1 January 1965 to 1 January 2006 without language selection. The medical subject heading (MeSH) and textwords for the following terms were used: hysteroscopy, diagnosis, histology, histopathology, hysterectomy, biopsy, sensitivity and specificity.
Setting University Hospital.
Selection criteria The inclusion criteria were report on accuracy of diagnostic hysteroscopy in women with abnormal uterine bleeding compared to histology collected with guided biopsy during hysteroscopy, operative hysteroscopy or hysterectomy.
Data collection and analysis Electronic databases were searched for relevant studies and references were cross‐checked. Validity was assessed and data were extracted independently by two authors. Heterogeneity was calculated and data were pooled. Subgroup analysis was performed according to validity criteria, study quality, menopausal state, time, setting and performance of the procedure. The pooled sensitivity, specificity, likelihood ratios, post‐test probabilities and feasibility of diagnostic hysteroscopy on the prediction of uterine cavity abnormalities. Post‐test probabilities were derived from the likelihood ratios and prevalence of intrauterine abnormalities among included studies. Feasibility included technical success rate and complication rate.
Main results One population of homogeneous data could be identified, consisting of patients with postmenopausal bleeding. In this subgroup the positive and negative likelihood ratios were 7.9 (95% CI 4.79–13.10) and 0.04 (95% CI 0.02–0.09), raising the pre‐test probability from 0.61 to a post‐test probability of 0.93 (95% CI 0.88–0.95) for positive results and reducing it to 0.06 (95% CI 0.03–0.13) for negative results. The pooled likelihood ratios of all studies included, calculated with the random effects model, were 6.5 (95% CI 4.1–10.4) and 0.08 (95% CI 0.07–0.10), changing the pre‐test probability of 0.46 to post‐test probabilities of 0.85 (95% CI 0.78–0.90) and 0.07 (0.06–0.08) for positive and negative results respectively. Subgroup analyses gave similar results. The overall success rate of diagnostic hysteroscopy was estimated at 96.9% (SD 5.2%, range 83–100%).
Conclusions This systematic review and meta‐analysis shows that diagnostic hysteroscopy is both accurate and feasible in the diagnosis of intrauterine abnormalities.
The Late Cretaceous–Early Paleogene is the most recent period in Earth history that experienced sustained global greenhouse warmth on multimillion year timescales. Yet, knowledge of ambient climate ...conditions and the complex interplay between various forcing mechanisms are still poorly constrained. Here we present a 14.75 million‐year‐long, high‐resolution, orbitally tuned record of paired climate change and carbon‐cycling for this enigmatic period (~67–52 Ma), which we compare to an up‐to‐date compilation of atmospheric pCO2 records. Our climate and carbon‐cycling records, which are the highest resolution stratigraphically complete records to be constructed from a single marine site in the Atlantic Ocean, feature all major transient warming events (termed “hyperthermals”) known from this time period. We identify eccentricity as the dominant pacemaker of climate and the carbon cycle throughout the Late Maastrichtian to Early Eocene, through the modulation of precession. On average, changes in the carbon cycle lagged changes in climate by ~23,000 years at the long eccentricity (405,000‐year) band, and by ~3,000–4,500 years at the short eccentricity (100,000‐year) band, suggesting that light carbon was released as a positive feedback to warming induced by orbital forcing. Our new record places all known hyperthermals of the Late Maastrichtian–Early Eocene into temporal context with regards to evolving ambient climate of the time. We constrain potential carbon cycle influences of Large Igneous Province volcanism associated with the Deccan Traps and North Atlantic Igneous Province, as well as the sensitivity of climate and the carbon‐cycle to the 2.4 million‐year‐long eccentricity cycle.
Plain Language Summary
The study of globally warm climates and short‐lived warming events in Earth's past can provide unrivaled insights into the challenges that mankind may face over the next few generations. Using samples recovered from an ocean drill core in the deep South Atlantic, we have generated continuous temperature and carbon cycle records from the calcite shells of a single microfossil species, spanning a period of globally warm climate from 67 to 52 million years ago, before the development of permanent large‐scale polar ice sheets. Our record contains a number of rapid warming events, allowing us to determine their origin. We find that changes in the shape of Earth's orbit around the Sun initiated warming at Earth's surface, which was then amplified by the release of greenhouse gases from temperature‐ or climate‐sensitive carbon stores (e.g., peat, permafrost, or methane hydrates). These rapid warming events increased in frequency and magnitude during the warmer climate intervals characterized by significant volcanic activity, suggesting that such carbon stores become more unstable during warmer climates. As our climate warms at unprecedented rates, the release of greenhouse gases from naturally occurring temperature‐ or climate‐sensitive carbon stores could also form an additional and largely unconstrained contribution to future climate change.
Key Points
405‐ and 100‐kyr eccentricity forced the climate and carbon cycle, with carbon cycle perturbations lagging climate during this time
Elevated global temperatures and atmospheric pCO2 during LIP volcanism increased climate and carbon cycle sensitivity to orbital forcing
The frequency of hyperthermals suggests that carbon was periodically released from a dynamic reservoir which could be replenished quickly
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